Background
Septic shock is a leading cause of mortality in critically ill patients. Despite recent advances in the understanding of septic shock pathophysiology, its management remains a therapeutic challenge.
Aim
We aimed to investigate the effects of partial and selective cyclooxygenase (COX)-2 inhibition without affecting constitutive COX-1 and basal COX-2 activities in septic rats induced by single cecal ligation and puncture (SCLP).
Materials and methods
A total of 24 Sprague Dawley rats were allocated into four groups: sham, SCLP, sham+celecoxib, and SCLP+celecoxib. At 2 h after sham and SCLP operations, celecoxib (0.5 mg/kg) or vehicle (saline; 1 ml/kg) was administered orally to rats. At 18 h after drug administrations, mesenteric artery blood flow and aortic activity were measured. Blood and tissue samples were obtained for biochemical and histopathological examinations. Furthermore, survival rate was monitored throughout 96 h.
Results
Celecoxib ameliorated mesenteric perfusion and aortic activity. Survival rate was 0% at 49th hour in the SCLP group, but in the SCLP+celecoxib group, it was 42.8% at the end of 96 h. Celecoxib prevents the increase of serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, blood urea nitrogen, creatinine, and inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 levels). The decreases in tissues glutathione levels and the increases in liver, lung, spleen, and kidney malondialdehyde levels in the SCLP group were prevented by celecoxib. The histopathological protective effects of celecoxib on organ injury owing to SCLP were also observed.
Conclusion
Celecoxib showed improvement of clinical outcomes of sepsis through effects on mesenteric perfusion, aortic function, and its anti-inflammatory and antioxidative effects.